Dental caries is a multi-factorial disease in which the virulence of microbes in the plaque biofilm, salivary function and diet and nutrition play important roles. We hypothesize that salivary components of both mammalian and non-mammalian origin are associated with risk for the development of dental caries. It is speculated that no single salivary component is important than the others, rather each of these components interact in a concerted fashion and a cumulative effect is important in protecting against caries. We will develop sandwich enzyme-linked immunoassays (ELISA) to quantitate the levels of salivary mucins MG1 and MG2; acidic proline- rich proteins 1 and 3, basic proline-rich proteins PRB-1 and PRB-2; glycosylated proline-rich protein PRG; cystatins S and SN; statherin; histatins 1, 3 and 5; lysozyme; lactoferrin and peroxidase; microbial enzymes glucosyltransferase and glucosyltransferase from Streptococcus mutans; and food preservative benzoate in a large number of subjects. We have already accumulated more than 4000 samples of resting whole saliva. The data obtained will be analyzed for the intra-subject stability of the analyte levels; the cross-sectional association of the decay, missing, filled surfaces (DMFS) index of the subjects analyte levels; and the longitudinal association of the DMFS with salivary analyte levels. The comprehensive survey and the cluster analysis of multiple salivary components should generate a useful data set to test for the association of these components with the caries experience and to identify parameters that will indicate increased risk for dental caries. This study will also provide useful information to determine whether there is a clinical relationship between benzoate levels in saliva and caries experience.